Biodistribution of cerium dioxide and titanium dioxide nanomaterials in rats after single and repeated inhalation exposures.

BACKGROUND: Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation. The aim of the present study was therefore to acquire two comparable datasets to parametrize a physiologically-based kinetic model. METHOD: Rats were exposed to cerium dioxide (CeO2, 28.4 ± 10.4 nm) and titanium dioxide (TiO2, 21.6 ± 1.5 nm) ENMs in a single nose-only exposure to 20 mg/m3 or a repeated exposure of 2 × 5 days to 5 mg/m3. Different dose levels were obtained by varying the exposure time for 30 min, 2 or 6 h per day. The content of cerium or titanium in three compartments of the lung (tissue, epithelial lining fluid and freely moving cells), mediastinal lymph nodes, liver, spleen, kidney, blood and excreta was measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at various time points post-exposure. As biodistribution is best studied at sub-toxic dose levels, lactate dehydrogenase (LDH), total protein, total cell numbers and differential cell counts were determined in bronchoalveolar lavage fluid (BALF). RESULTS: Although similar lung deposited doses were obtained for both materials, exposure to CeO2 induced persistent inflammation indicated by neutrophil granulocytes influx and exhibited an increased lung elimination half-time, while exposure to TiO2 did not. The lavaged lung tissue contained the highest metal concentration compared to the lavage fluid and cells in the lavage fluid for both materials. Increased cerium concentrations above control levels in secondary organs such as lymph nodes, liver, spleen, kidney, urine and faeces were detected, while for titanium this was found in lymph nodes and liver after repeated exposure and in blood and faeces after a single exposure. CONCLUSION: We have provided insight in the distribution kinetics of these two ENMs based on experimental data and modelling. The study design allows extrapolation at different dose-levels and study durations. Despite equal dose levels of both ENMs, we observed different distribution patterns, that, in part may be explained by subtle differences in biological responses in the lung.

Bacterial Susceptibility to Ceria Nanoparticles: The Critical Role of Surrounding Molecules.

Investigating the ternary relationship among nanoparticles (NPs), their immediate molecular environment, and test organisms rather than the direct interaction between pristine NPs and test organisms has been thrust into the mainstream of nanotoxicological research. Diverging from previous work that predominantly centered on surrounding molecules affecting the toxicity of NPs by modulating their nanoproperties, this study has unveiled a novel dimension: surrounding molecules altering bacterial susceptibility to NPs, consequently impacting the outcomes of nanobio interaction. The study found that adding nitrate as the surrounding molecules could alter bacterial respiratory pathways, resulting in an enhanced reduction of ceria NPs (nanoceria) on the bacterial surfaces. This, in turn, increased the ion-specific toxicity originating from the release of Ce3+ ions at the nanobio interface. Further transcriptome analysis revealed more mechanistic details underlying the nitrate-induced changes in the bacterial energy metabolism and subsequent toxicity patterns. These findings offer a new perspective for the deconstruction of nanobio interactions and contribute to a more comprehensive understanding of NPs' environmental fate and ecotoxicity.

Effect of CeO2, TiO2 and SiO2 nanoparticles on the growth and quality of model medicinal plant Salvia miltiorrhiza by acting on soil microenvironment.

In this study, a six-month pot experiment was conducted to explore the effects of nanoparticles (NPs), including CeO2, TiO2 and SiO2 NPs at 200 and 800 mg/kg, on the growth and quality of model medicinal plant Salvia miltiorrhiza. A control group was implemented without the application of NPs. Results showed that NPs had no significant effect on root biomass. Treatment with 200 mg/kg of SiO2 NPs significantly increased the total tanshinone content by 44.07 %, while 200 mg/kg of CeO2 NPs were conducive to a 22.34 % increase in salvianolic acid B content. Exposure to CeO2 NPs induced a substantial rise in the MDA content in leaves (176.25 % and 329.15 % under low and high concentration exposure, respectively), resulting in pronounced oxidative stress. However, TiO2 and SiO2 NPs did not evoke a robust response from the antioxidant system. Besides, high doses of CeO2 NP-amended soil led to reduced nitrogen, phosphorus and potassium contents. Furthermore, the NP amendment disturbed the carbon and nitrogen metabolism in the plant rhizosphere and reshaped the rhizosphere microbial community structure. The application of CeO2 and TiO2 NPs promoted the accumulation of metabolites with antioxidant functions, such as D-altrose, trehalose, arachidonic acid and ergosterol. NPs displayed a notable suppressive effect on pathogenic fungi (Fusarium and Gibberella) in the rhizosphere, while enriching beneficial taxa with disease resistance, heavy metal antagonism and plant growth promotion ability (Lysobacter, Streptomycetaceae, Bacillaceae and Hannaella). Correlation analysis indicated the involvement of rhizosphere microorganisms in plant adaptation to NP amendments. NPs regulate plant growth and quality by altering soil properties, rhizosphere microbial community structure, and influencing plant and rhizosphere microbe metabolism. These findings were beneficial to deepening the understanding of the mechanism by which NPs affect medicinal plants.

Alginate and chitosan surface coating reduces the phytotoxicity of CeO2 nanoparticles to duckweed (Lemna minor L.).

Little is known about the effect of surface coatings on the fate and toxicity of CeO2 nanoparticles (NPs) to aquatic plants. In this study, we modified nCeO2 with chitosan (Cs) and alginate (Al) to obtain positively charged nCeO2@Cs and negatively charged nCeO2@Al, respectively, and exposed them to a representative aquatic plant, duckweed (Lemna minor L.). Uncoated nCeO2 could significantly inhibit the growth of duckweed, induce oxidative damage and lead to cell death, whereas nCeO2@Cs and nCeO2@Al exhibited lower toxicity to duckweed. ICP-MS analysis revealed that the Ce content in duckweed from the nCeO2 group was 1.74 and 2.85 times higher than that in the nCeO2@Cs and nCeO2@Al groups, respectively. Microscopic observations indicated that the positively charged nCeO2@Cs was more readily adsorbed on the root surface of duckweed than the negatively charged nCeO2@Al. The results of XANES and LCF demonstrated that a certain percentage of Ce(Ⅳ) was reduced to Ce(Ⅲ) after the interaction of the three NPs with duckweed, but the degree of biotransformation differed among the treatments. Specifically, the absolute contents of Ce(III) produced of nCeO2@Cs and nCeO2@Al through biotransformation were reduced by 55.5% and 83.5%, respectively, compared with that of the nCeO2 group, which might be the key factor for the diminished phytotoxicity of the coated nCeO2 to the duckweed. These findings were valuable for understanding the toxicity of metal-based NPs to aquatic plants and for the synthesis of environmentally friendly nanomaterials.

Effect of interactions between humic acid and cerium oxide nanoparticles on the toxicity to the Chlorella sp.

With the wide application of nanomaterials, the concentration of nanomaterials in natural water continues to increase, which poses a severe threat to the water environment. However, the influence of organic matter and nanomaterials rich in natural water on the toxic effect of algae growth is still unclear. In this study, the effects of humic acid (HA) and nano-cerium oxide (nCeO2) on the physiology and transcriptome of Chlorella sp. were analyzed, and the mechanism of the toxic effect of HA on Chlorella sp. under nCeO2 stress was revealed. Under 20-200 mg/L nCeO2 stress, the growth of Chlorella cells was inhibited and the highest inhibition rate reached 52% within 200 mg/L nCeO2. The Fv/Fm and ETRmax values of Chlorella sp. decreased from 0.490 and 24.45 (20 mg/L nCeO2) to 0.488 and 23.4 (100 mg/L nCeO2), respectively. Under the stimulation of nCeO2, the level of reactive oxygen species in algal cells was increased, accompanied by lipid peroxidation and membrane damage. However, the addition of HA at concentrations of 5-10 mg/L effectively alleviated the toxic effect of nCeO2 on Chlorella sp. Transcriptome analysis showed that 10 mg/L HA could alleviate the cellular stress at 100 mg/L nCeO2 on Chlorella sp. by regulating genes related to photosynthesis and metabolism pathways. Moreover, the downregulation of genes (e.g., Lhca1, Lhcb1, AOC3, and AOC2) indicated that HA reduced the level of oxidative stress in Chlorella sp. These findings offer novel insights of evaluating the ecotoxicity nCeO2 and HA in natural water environment and their impact on Chlorella sp.

Ceria nanoparticles: biomedical applications and toxicity. / 二氧化铈纳米颗粒：生物医学应用和毒性.

Ceria nanoparticles (CeO2 NPs) have become popular materials in biomedical and industrial fields due to their potential applications in anti-oxidation, cancer therapy, photocatalytic degradation of pollutants, sensors, etc. Many methods, including gas phase, solid phase, liquid phase, and the newly proposed green synthesis method, have been reported for the synthesis of CeO2 NPs. Due to the wide application of CeO2 NPs, concerns about their adverse impacts on human health have been raised. This review covers recent studies on the biomedical applications of CeO2 NPs, including their use in the treatment of various diseases (e.|g., Alzheimer's disease, ischemic stroke, retinal damage, chronic inflammation, and cancer). CeO2 NP toxicity is discussed in terms of the different systems of the human body (e.|g., cytotoxicity, genotoxicity, respiratory toxicity, neurotoxicity, and hepatotoxicity). This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

Nano-CeO2 activates physical and chemical defenses of garlic (Allium sativum L.) for reducing antibiotic resistance genes in plant endosphere.

The transmission of manure- and wastewater-borne antibiotic-resistant bacteria (ARB) to plants contributes to the proliferation of antimicrobial resistance in agriculture, necessitating effective strategies for preventing the spread of antibiotic resistance genes (ARGs) from ARB in the environment to humans. Nanomaterials are potential candidates for efficiently controlling the dissemination of ARGs. The present study investigated the abundance of ARGs in hydroponically grown garlic (Allium sativum L.) following nano-CeO2 (nCeO2) application. Specifically, root exposure to nCeO2 (1, 2.5, 5, 10 mg L-1, 18 days) reduced ARG abundance in the endosphere of bulbs and leaves. The accumulation of ARGs (cat, tet, and aph(3')-Ia) in garlic bulbs decreased by 24.2-32.5 % after nCeO2 exposure at 10 mg L-1. Notably, the lignification extent of garlic stem-disc was enhanced by 10 mg L-1 nCeO2, thereby accelerating the formation of an apoplastic barrier to impede the upward transfer of ARG-harboring bacteria to garlic bulbs. Besides, nCeO2 upregulated the gene expression related to alliin biosynthesis and increased allicin content by 15.9-16.2 %, promoting a potent antimicrobial defense for reducing ARG-harboring bacteria. The potential exposure risks associated with ARGs and Ce were evaluated according to the estimated daily intake (EDI). The EDI of ARGs exhibited a decrease exceeding 95 %, while the EDI of Ce remained below the estimated oral reference dose. Consequently, through stimulating physical and chemical defenses, nCeO2 contributed to a reduced EDI of ARGs and Ce, highlighting its potential for controlling ARGs in plant endosphere within the framework of nano-enabled agrotechnology.

Safety assessment and gastrointestinal retention of orally administered cerium oxide nanoparticles in rats.

Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the "no observed adverse effect level" of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.

The cerium oxide nanoparticles toxicity induced physiological, histological and biochemical alterations in freshwater mussels, Unio crassus.

INTRODUCTION: Releasing of cerium oxide nanoparticles (nano-CeO2) to the nature has increased due to the widespread use in many fields ranging from cosmetics to the food industry. Therefore, nano-CeO2 has been included in the Organization for Economic Co-operation and Development's (OECD) priority list for engineering nanomaterials. In this study, the effects of nano-CeO2 on the freshwater mussels were investigated to reveal the impact on the freshwater systems on model organism. METHODS: First, the chemical and structural properties of nano-CeO2 were characterized in details. Second, the freshwater mussels were exposed to environmentally relevant concentrations of nano-CeO2 as 10 mg, 25 mg and 50 mg/L during 48-h and 7-d. Third, after the exposure periods, hemolymph and tissue samples were taken to analyse the Total Hemocyte Counts (THCs) histology and oxidative stress parameters (total antioxidant status, glutathione, glutathione-S-transferase, and advanced oxidative protein products). RESULTS: Significant decrease of the THCs was observed in the nano-CeO2 exposed mussels compared to the control group (P < 0.05). The histological results showed a positive association between nano-CeO2 exposure concentration in the water and level of tissue damage and histopathological alterations were detected in the gill and the digestive gland tissues. Oxidative stress parameters were slightly affected after exposure to nano-CeO2 (P > 0.05). In conclusion, this study showed that acute exposure of freshwater mussels to nano-CeO2 did not pose significant biological risk. However, it has been proven that mussels are able to accumulate nano-CeO2 significantly in their bodies. CONCLUSION: This suggests that nano-CeO2 may be a potential risk to other organisms in the ecosystem through trophic transfer in the food-web based on their habitat and niche in the ecosystem.

Toxicokinetics of praseodymium and cerium administered as chloride salts in Sprague-Dawley rats: impacts of the dose and of co-exposure with additional rare earth elements.

We conducted a rat exposure study to assess the impacts of dose and co-exposure with other rare earth elements (REEs) on the toxicokinetics of praseodymium (Pr) and cerium (Ce). We first determined the kinetic profiles of elemental Pr and Ce in blood, urine and feces along with tissue levels at sacrifice on the seventh day following intravenous injection of PrCl3 or CeCl3 at 0.3 or 1 mg/kg bw (of the chloride salts) in adult male Sprague-Dawley rats (n = 5 per group). In blood, Pr and Ce half-lives for the initial phase (t1/2α) increased with increasing doses, while their half-lives for the terminal phase (t1/2ß) were similar at both doses. In urine, a minor excretion route, no significant effect of the dose on the cumulative excretion was apparent. In feces, a major excretion route, the fraction of the Pr dose recovered was significantly lower at the 1 mg/kg bw dose compared to the 0.3 mg/kg bw dose, while no significant dose effect was apparent for Ce. In the liver and spleen, which are the main sites of REEs accumulation, there was a significant effect of the dose only for Ce retention in the spleen (i.e., increased retention of Ce in spleen at higher dose). Results were compared with those of a previous toxicokinetic study with a similar design but an exposure to a quaternary mixture of CeCl3, PrCl3, NdCl3 and YCl3, each administered at 0.3 mg/kg bw or 1 mg/kg bw. A mixture effect was apparent for the initial elimination phase (t1/2α) of Pr and Ce from blood and for the fecal excretion of Ce at the 1 mg/kg bw. In urine and liver, there was no evident overall mixture effect; in the spleen, there was a higher retention of Pr and Ce in rats exposed to the mixture at the 0.3 mg/kg bw, but not at the 1 mg/kg bw dose. Overall, this study showed that the dose and mixture exposure are two important factors to consider as determinants of the toxicokinetics of REEs.

The effect of gibberellic acid on wheat growth and nutrient uptake under combined stress of cerium, zinc and titanium dioxide nanoparticles.

Nanoparticles (NPs) are released and dispersed in the environment because of increased manufacturing and use of nano products. NPs disturb the growth of plants depending upon types, exposure duration and plant species. The purpose of this research was to explore the role of gibberellic acid (GA) exposure through foliar route on wheat growth under alone or combined soil application of cerium oxide (CeO2), zinc oxide (ZnO), and titanium dioxide (TiO2) NPs. GA was foliar-applied (200 mg/L) on the wheat plants treated with individual and in all possible combination of the selected NPs. Explorations have revealed that the combination of NPs and GA worked well to enhance the plant growth and selected nutrient status than NPs alone. Furthermore, GA decreased the boosted antioxidant enzyme activities under the combination and individual NPs compared to the alone NPs treated plants, lowered the oxidative stress in wheat plants which provided the additional proof that GA decreased oxidative damage in plants. Combined NPs showed differential effects than individual NPs application irrespective of GA exposure which varied with NPs combination and studied parameters of plants. GA + NPs differentially affected the potassium, phosphorus, iron and manganese concentrations in wheat tissues than NPs alone treatments. Overall, GA can be applied when there is excess of NPs (either alone or in combination) in the growth medium to ensure the growth of crops. However, further studied are needed with other plant species and alone or combined use of different NPs under GA treatment before any final recommendation.

Combined cerium and zinc oxide nanoparticles induced hepato-renal damage in rats through oxidative stress mediated inflammation.

The toxicity profiles of nanoparticles (NPs) used in appliances nowadays remains unknown. In this study, we investigated the toxicological consequences of exposure to cerium oxide (CeO2) and zinc oxide (ZnO) nanoparticles given singly or in combination on the integrity of liver and kidney of male Wistar rats. Twenty (20) rats were allotted into four groups and treated as: Control (normal saline), CeO2NPs (50 µg/kg), ZnONPs (80 µg/kg) and [CeO2NPs (50 µg/kg) + ZnONPs (80 µg/kg)]. The nanoparticles were given to the animals through the intraperitoneal route, three times per week for four repeated weeks. Results revealed that CeO2 and ZnO NPs (singly) increased serum AST and ALT by 29% & 57%; 41% & 18%, and co-administration by 53% and 23%, respectively. CeO2 and ZnO NPs increased hepatic and renal malondialdehyde (MDA) by 33% and 30%; 38% and 67%, respectively, while co-administration increased hepatic and renal MDA by 43% and 40%, respectively. The combined NPs increased hepatic NO by 28%. Also, CeO2 and ZnO NPs, and combined increased BAX, interleukin-1ß and TNF-α by 45, 38, 52%; 47, 23, 82% and 41, 83, 70%, respectively. Histology revealed hepatic necrosis and renal haemorrhagic parenchymal in NPs-treated rats. Summarily, CeO2 and ZnO NPs produced oxidative injury and induced inflammatory process in the liver and kidney of experimental animals.

Benzo(a)pyrene and Cerium Dioxide Nanoparticles in Co-Exposure Impair Human Trophoblast Cell Stress Signaling.

Human placenta is a multifunctional interface between maternal and fetal blood. Studying the impact of pollutants on this organ is crucial because many xenobiotics in maternal blood can accumulate in placental cells or pass into the fetal circulation. Benzo(a)pyrene (BaP) and cerium dioxide nanoparticles (CeO2 NP), which share the same emission sources, are found in ambient air pollution and also in maternal blood. The aim of the study was to depict the main signaling pathways modulated after exposure to BaP or CeO2 NP vs. co-exposure on both chorionic villi explants and villous cytotrophoblasts isolated from human term placenta. At nontoxic doses of pollutants, BaP is bioactivated by AhR xenobiotic metabolizing enzymes, leading to DNA damage with an increase in γ-H2AX, the stabilization of stress transcription factor p53, and the induction of its target p21. These effects are reproduced in co-exposure with CeO2 NP, except for the increase in γ-H2AX, which suggests a modulation of the genotoxic effect of BaP by CeO2 NP. Moreover, CeO2 NP in individual and co-exposure lead to a decrease in Prx-SO3, suggesting an antioxidant effect. This study is the first to identify the signaling pathways modulated after co-exposure to these two pollutants, which are common in the environment.

Hormetic Effects of Cerium, Lanthanum and Their Combination at Sub-micromolar Concentrations in Sea Urchin Sperm.

Rare earth elements (REEs) cerium (Ce) and lanthanum (La) and their combination were tested across a concentration range, from toxic (10-4 to 10-5 M) to lower concentrations (10-6 to 10-8 M) for their effects on sea urchin (Sphaerechinus granularis) sperm. A significantly decreased fertilization rate (FR) was found for sperm exposed to 10-5 M Ce, La and their combination, opposed to a significant increase of FR following 10-7 and 10-8 M REE sperm exposure. The offspring of REE-exposed sperm showed significantly increased developmental defects following sperm exposure to 10-5 M REEs vs. untreated controls, while exposure to 10-7 and 10-8 M REEs resulted in significantly decreased rates of developmental defects. Both of observed effects-on sperm fertilization success and on offspring quality-were closely exerted by Ce or La or their combination.

Maternal cerium nitrate exposure induces developmental immunotoxicity in BALB/c mouse offspring.

With the increasing application of cerium and rare-earth elements (REEs), cerium exposure is becoming more widespread. However, there remains a paucity of evidence on developmental immunotoxicity of cerium. This study was designed to examine the developmental immunotoxicity of gestational and postnatal exposure to cerium nitrate (CN) in BALB/C mouse offspring. Dams were given CN by oral gavage at 0, 0.002, 0.02 and 0.2 mg/kg from gestation day 5 (GD5) to postnatal day 21 (PND 21). On PND 21, the highest dose of CN significantly suppressed the NK cell cytotoxicity, and reduced the proportions of NK cells in peripheral blood and spleen of both female and male pups, however, the proportions of monocytes in peripheral blood and macrophages in spleen only increased in female pups. For adaptive immunity, on PND 21, the suppression of T/B lymphocyte proliferation, humoral and cellular immune responses (number of splenic plaque-forming cells, PFC, and delayed-type hypersensitivity, DTH) were observed in both female and male pup mice exposed to 0.2 mg/kg CN. However, the fall of proportions of T/B lymphocytes in peripheral blood (PB), spleen and mesenteric lymph node (MLN) only found in female pups at 0.2 mg/kg on PND 21. Most indications recovered to normal after 3-week cessation of CN exposure, except the reduction of DTH and PFC. From the findings in this study, the lowest-observed-adverse-effect level (LOAEL) of CN for developmental immunotoxicity was estimated to be 0.2 mg/kg bw per day.

Divergent responses and ecological risks of wheat (Triticum aestivum L.) to cerium oxide nanoparticles in different soil types.

Cerium oxide nanoparticles (nCeO2), as a common component for sustainable agriculture, have been broadly investigated due to their potential threat to the soil biodiversity and health. However, few studies considered the impacts of soil types on response of ecotoxicity of nCeO2 to plants. This study aimed to explore the effects of soil properties on ecological response of nCeO2 to wheat (Triticum aestivum L.) and assess the ecological risks of nCeO2 (0-1000 mg/kg) in red soil, yellow-brown soil, and brown soil by applying a multi-biomarker approach. The results showed that the clay content had the extremely significant correlation with acid solute fraction Ce in soil. Ce accumulation in wheat largely depended on acid-soluble fraction Ce, but not the total Ce. Both urease and invertase activities were highest in brown soil among the three soils, after exposure to diverse concentration nCeO2. Although wheat has a stronger antioxidant capacity in red soil, integrated biomarker response index proved that nCeO2 showed least toxicity to wheat in brown soil (IBRv2 = 34.3) among the three soils. These results indicated that the toxicity level of nCeO2 to wheat was not only related to contaminated concentration, but also greatly depended on soil properties. The soil types are important factors governing ecological risk of nCeO2 in soil, which needs to be adequately assessed and properly controlled.

Selenium nanoparticles reduce Ce accumulation in grains and ameliorate yield attributes in mung bean (Vigna radiata) exposed to CeO2.

Exposure of crops to CeO2 nanoparticles (nCeO2) in agricultural environments impact crop quality and human health. In this regard, the effects of selenium nanoparticles (nSe) on the yield and quality of Vigna radiata (L.) exposed to nCeO2 were investigated. The experiment was carried out as a factorial with two factors: NPs (nCeO2, and nSe) as factor one and concentrations as factor two [(0, 250, 500 and 1000 mg/L nCeO2; 0, 25, 50 and 75 mg/L nSe)]. Nanoparticles were foliar applied to 45-day old mung bean shoot in two steps and one-week interval. At 250-1000 mg/L, nCeO2 increased P, protein and Ce accumulation in grain. Additionally, at 1000 mg/L, the nCeO2, significantly decreased seed number, yield, Fe, and Zn storage in seeds. Conversely, at 25 and 50 mg/L, nSe stimulated the growth and yield of mung bean, and significantly increased P, Fe, Zn, and Se in seeds, but reduced the protein content in seeds. The Se25+Ce250 and Se50+Ce250 significantly increased pod number, seed number, grain weight, yield, Fe, Zn and Se storage in grains. In contrast, the Ce accumulation in seeds decreased in all combination treatments (nCeO2 + nSe) compared to their respective single nCeO2 treatments. Moreover, in the plants exposed to high nCeO2 concentrations, nSe application resulted in undamaged vacuoles, less starch granules' accumulation, significant yield improvement, and elevated Fe, Se, and Zn in seeds. Data suggest that selenium nanoparticles prevent nCeO2 stress in mung bean and improve grain production and quality.

Uptake and toxicity of cerium dioxide nanoparticles with different aspect ratio.

Cerium dioxide nanoparticles (CeONPs) have been extensively applied in research for future energy development due to two common oxidation states on their surface. Considering that shape (aspect ratio) is a key determinant of NPs-induced toxicity, we compared the toxicity of hexagonal (H)- and rod-shaped (R)-CeONPs in mice. At 24 h after pharyngeal aspiration, both types of CeONPs recruited surrounding immune cells (monocytes and neutrophils) into the lung, and R-CeONPs induced a more severe pulmonary inflammatory response compared with H-CeONPs. To identify an indicator to predict pulmonary inflammatory responses at the cellular level, we also investigated their responses in alveolar macrophage cells. At 24 h after treatment, both types of CeONPs were mainly located within the vacuoles (partially, in the lysosome) in the cytoplasm. Mitochondrial damage, intracellular calcium accumulation, and increased NO production were observed in cells exposed to both types of CeONPs, ultimately resulting in a decrease in cell viability. More interestingly, both types of CeONPs formed multinucleated giant cells. Meanwhile, contrary to when suspended in deionized water, R-CeONPs were strongly aggregated with a negative charge in cell culture media, whereas H-CeONPs were relatively well-dispersed with a positive charge. R-CeONPs-induced lysosomal extension was also recovered by premix with negatively charged DNA, and even NPs suspended in cell culture media without cells were detected under the FACS system, suggesting interference by protein corona. Therefore, we suggest that shape (aspect ratio) is an important factor determining inhaled NPs-induced pathology and that the effect of the surface charge and protein corona should be carefully considered in interpreting results derived from in vitro tests. Furthermore, we propose that the relationship between the formation of multinucleated giant cells and the inflammatory response of inhaled CeONPs should be further studied.

Mechanisms of cerium-induced stress in plants: A meta-analysis.

A comprehensive evaluation of the effects of cerium on plants is lacking even though cerium is extensively applied to the environment. Here, the effects of cerium on plants were meta-analyzed using a newly developed database consisting of approximately 8500 entries of published data. Cerium affects plants by acting as oxidative stressor causing hormesis, with positive effects at low concentrations and adverse effects at high doses. Production of reactive oxygen species and its linked induction of antioxidant enzymes (e.g. catalase and superoxide dismutase) and non-enzymatic antioxidants (e.g. glutathione) are major mechanisms driving plant response mechanisms. Cerium also affects redox signaling, as indicated by altered GSH/GSSG redox pair, and electrolyte leakage, Ca2+, K+, and K+/Na+, indicating an important role of K+ and Na+ homeostasis in cerium-induced stress and altered mineral (ion) balance. The responses of the plants to cerium are further extended to photosynthesis rate (A), stomatal conductance (gs), photosynthetic efficiency of PSII, electron transport rate, and quantum yield of PSII. However, photosynthesis response is regulated not only by physiological controls (e.g. gs), but also by biochemical controls, such as via changed Hill reaction and RuBisCO carboxylation. Cerium concentrations <0.1-25 mg L-1 commonly enhance chlorophyll a and b, gs, A, and plant biomass, whereas concentrations >50 mg L-1 suppress such fitness-critical traits at trait-specific concentrations. There was no evidence that cerium enhances yields. Observations were lacking for yield response to low concentrations of cerium, whereas concentrations >50 mg Kg-1 suppress yields, in line with the response of chlorophyll a and b. Cerium affects the uptake and tissue concentrations of several micro- and macro-nutrients, including heavy metals. This study enlightens the understanding of some mechanisms underlying plant responses to cerium and provides critical information that can pave the way to reducing the cerium load in the environment and its associated ecological and human health risks.

Comparison of biodistribution of cerium oxide nanoparticles after repeated oral administration by gavage or snack in Sprague Dawley rats.

The rate of translocation of ingested nanoparticles (NPs) and how the uptake is affected by a food matrix are key aspects of health risk assessment. In this study, female Sprague Dawley rats (N = 4/group) received 0, 1.4, or 13 mg of cerium oxide (CeO2 NM-212) NPs/rat/day by gavage or in a chocolate spread snack 5 days/week for 1 or 2 weeks followed by 2 weeks of recovery. A dose and time-dependent uptake in the liver and spleen of 0.1-0.3 and 0.004-0.005 parts per million (ng/mg) of the total administered dose was found, respectively. There was no statistically significant difference in cerium concentration in the liver or spleen after gavage compared to snack dosing. Microscopy revealed indications of necrotic changes in the liver and decreased cellularity in white pulp in the spleen. The snack provided precise administration and a more human-relevant exposure of NPs and could improve animal welfare as alternative to gavage.